GBA2 p.Ala441=
c.1323A>T · rs148198188 · VCV697637
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.129%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.9 | GERP -3.8 |
| Overall | ||
| CADD | 2.915 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.129%
African / African-American · 97/74,978 alleles
Filtering AF
0.108%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.101%
Overall
0.00774%
125/1,613,992 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.129% | 773 |
| Admixed American | 0.0217% | 4,617 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,251 |
| European (non-Finnish) | 0.000424% | 235,993 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- GBA2
- Protein
- p.Ala441=
- Coding
- c.1323A>T
- MANE Select
- NM_020944
- dbSNP
- rs148198188
- Type
- single nucleotide variant
- Location
- chr9:35740084 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.77
- Residue 441
- a UniProt-annotated variant site (in spg46; loss of glucosylceramide catabolic process)
Similar variants
- GBA2 c.1582+2T>G Likely pathogenic ★★ same type
- GBA2 p.Arg234Ter Pathogenic ★★ same type
- GBA2 p.Arg340Ter Pathogenic ★★ same type
- GBA2 p.Arg574Ter Pathogenic ★★ same type
- GBA2 p.Arg630Trp Pathogenic/Likely pathogenic ★★ same type
- GBA2 p.Arg870Ter Likely pathogenic ★★ same type
- GBA2 p.Arg873His Pathogenic/Likely pathogenic ★★ same type
- GBA2 p.Ala187Thr Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/gba2-p-ala441 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown